Engineered proteins, such as multispecific binding proteins capable of binding two or more antigens, are known in the art. Such multispecific binding proteins can be generated using cell fusion, chemical conjugation, or recombinant DNA techniques. There are a variety of multispecific binding protein structures known in the art and many structures and methods have distinct disadvantages.
Bispecific antibodies have been produced using quadroma technology. However, the presence of mis-paired by-products and significantly reduced production yields with this technology means that sophisticated purification procedures are required. Bispecific antibodies can also be produced by chemical conjugation of two different mAbs. However, this approach does not yield homogeneous preparations.
Other approaches used previously include coupling of two parental antibodies with a hetero-bifunctional crosslinker, production of tandem single-chain Fv molecules, diabodies, bispecific diabodies, single-chain diabodies, and di-diabodies. However, each of these approaches have disadvantages. In addition, a multivalent antibody construct comprising two Fab repeats in the heavy chain of an IgG and capable of binding four antigen molecules has been described (see PCT Publication No. WO 0177342 and Miller et al. (2003) J. Immunol. 170(9): 4854-61).
U.S. Pat. No. 7,612,181 provides a novel family of binding proteins capable of binding two or more antigens with high affinity, which are called dual variable domain binding proteins (DVD binding protein) or dual variable domain immunoglobulins (DVD-Ig™).
While a variety of structures are provided in the art, some with advantages and disadvantages, specific constructs are required for preparing multivalent binding proteins with specific properties and which bind to specific targets. Additionally, new variable domain sequences can further improve the properties of the binding proteins.
Interleukin 13 (IL-13) is a 17-kDa glycoprotein produced by activated T cells of the Th2 lineage. The function of IL-13 includes immunoglobulin isotype switching to IgE in human B cells and suppressing inflammatory cytokine production. IL-13 is associated primarily with the induction of airway inflammation such as asthma. It has also been linked to other allergic diseases, fibrotic conditions, cancer and infectious diseases.
Interleukin-17 (IL-17, also referred to as IL-17A) is a 20-30 kD homodimeric glycoprotein secreted by activated T cells at the site of inflammation. IL-17 acts as a proinflammatory cytokine by inducing the production of multiple adhesion molecules, inflammatory cytokines and chemokines in various tissues to recruit monocytes and neutrophils to the site of inflammation. IL-17 also plays an important role in the maturation of hematopoietic progenitor cells. Inappropriate or excessive production of IL-17 is associated with the pathology of various diseases or disorders including rheumatoid arthritis, asthma, lupus, allograft rejection, other inflammatory or autoimmune diseases and cancer.
There is a need in the art for improved multivalent binding proteins capable of binding IL-13 and/or IL-17. Novel binding proteins that bind IL-13 and IL-17 are provided herein.